Fish Oil and the Pan-PPAR Agonist Tetradecylthioacetic Acid Affect the Amino Acid and Carnitine Metabolism in Rats
Fish Oil and the Pan-PPAR Agonist Tetradecylthioacetic Acid Affect the Amino Acid and Carnitine Metabolism in Rats
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DOI：
10.1371/journal.pone.0066926
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发表时间：
2013-06-24
期刊：
影响因子：
3.7
通讯作者：
Berge, Rolf Kristian
中科院分区：
文献类型：
--
作者：
Bjorndal, Bodil;Brattelid, Trond;Berge, Rolf Kristian
过氧化物酶体增殖物激活受体（PPARs）在脂质和葡萄糖代谢的调节中具有重要作用。近期研究表明，WY 14,643对PPARα的激活可调节氨基酸代谢。我们利用两种具有不同配体结合特性的PPARα激活剂——十四烷基硫代乙酸（TTA）和鱼油，研究了PPAR激活对血浆氨基酸水平的影响，其中泛PPAR激动剂TTA是一种比ω - 3多不饱和脂肪酸更强的配体。此外，还对血浆左旋肉碱酯进行了研究，以反映细胞脂肪酸的分解代谢。雄性Wistar大鼠（褐家鼠）被喂食含TTA（0.375%，w/w）、鱼油（10%，w/w）或两者组合的高脂肪（25% w/w）饲料。大鼠喂食50周，尽管TTA和鱼油对这些动物有降甘油三酯的作用，但与高脂肪对照组动物相比，只有TTA降低了体重增加。观察到鱼油和TTA对血浆氨基酸组成有明显的饮食影响。给予TTA导致除精氨酸和赖氨酸（降低）外的大多数氨基酸的血浆水平升高。然而，鱼油仅使少数几种氨基酸的血浆水平升高，两者组合显示出一种中间效应或TTA主导的效应。另一方面，TTA和鱼油相加地降低了左旋肉碱前体γ - 丁酰甜菜碱以及肉碱酯乙酰肉碱、丙酰肉碱、戊酰/异戊酰肉碱和辛酰肉碱的血浆水平。这些数据表明，虽然鱼油和TTA都影响脂质代谢，但需要强烈的PPARα激活才能对血浆氨基酸水平产生影响。TTA和鱼油可能通过不同的代谢机制影响氨基酸代谢。
Peroxisome proliferator-activated receptors (PPARs) are important in the regulation of lipid and glucose metabolism. Recent studies have shown that PPAR alpha-activation by WY 14,643 regulates the metabolism of amino acids. We investigated the effect of PPAR activation on plasma amino acid levels using two PPAR alpha activators with different ligand binding properties, tetradecylthioacetic acid (TTA) and fish oil, where the pan-PPAR agonist TTA is a more potent ligand than omega-3 polyunsaturated fatty acids. In addition, plasma L-carnitine esters were investigated to reflect cellular fatty acid catabolism. Male Wistar rats (Rattus norvegicus) were fed a high-fat (25% w/w) diet including TTA (0.375%, w/w), fish oil (10%, w/w) or a combination of both. The rats were fed for 50 weeks, and although TTA and fish oil had hypotriglyceridemic effects in these animals, only TTA lowered the body weight gain compared to high fat control animals. Distinct dietary effects of fish oil and TTA were observed on plasma amino acid composition. Administration of TTA led to increased plasma levels of the majority of amino acids, except arginine and lysine, which were reduced. Fish oil however, increased plasma levels of only a few amino acids, and the combination showed an intermediate or TTA-dominated effect. On the other hand, TTA and fish oil additively reduced plasma levels of the L-carnitine precursor gamma-butyrobetaine, as well as the carnitine esters acetylcarnitine, propionylcarnitine, valeryl/isovalerylcarnitine, and octanoylcarnitine. These data suggest that while both fish oil and TTA affect lipid metabolism, strong PPAR alpha activation is required to obtain effects on amino acid plasma levels. TTA and fish oil may influence amino acid metabolism through different metabolic mechanisms.